Pyrethroids

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Pyrethroids
Melissa Hardstone mch38_at_cornell.edu March 10, 2008
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Why do we care?

• Currently make up 20 of the total volume of
  insecticides used all over the world
• Low mammalian toxicity
• 2 class of insecticide used today (OPs are 1)

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Discovery and history

• Early 1800s housewives in Persia would keep
  dried flowers around to kill insects (cultivation
  starts in 1840)
• 1860 - pyrethrum powder exported to the United
  States
• 1914 - due to World War I, the cultivation of
  pyrethrum is suspended in Persia, with Japan
  slowly taking over the market
• 1919 - pyrethrum import in the United States
  reaches 1000 tons per year, kerosine extracts
  replace powder in home use

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• 1924 - identification of the active substances
  structure from pyrethrum extract
• 1928 - the use of pyrethrum powder almost ceases
• 1945 - Kenya is the world's main pyrethrum
  producer (and still is)
• 1972 - world pyrethrum production amounted to
  more than 21,000 tons (with production in Kenya,
  Tanzania, Rwanda, Ecuador and Japan)

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Botanical Chrysanthemum cinerariaefolium

• Flowers are harvested by hand, dried, and
  extracted
• Extracted product contains 1-3 pyrethrins by
  dry weight (3-4 mg pyrethrins/flower)
• Casida (1980) Envir. Health Persp.
• Remainder of product is made of waxes and
  pigments
• Pyrethrins are especially good for knockdown of
  insects

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Development/Manufacturing

• 1960s Dr. Casida in Berkeley
• Identified major pathways of breakdown of
  pyrethrins and early pyrethroids
• 1960s and 1970s Era of synthesis
• Pyrethroids take 2nd place as most widely used
  class, beating out carbamates
• 1980-1997 Commercial development begins
• Dr. Elliott _at_ Rothamsted, Sumitomo, Roussel UCLAF

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Whats in the crude extract
68
22
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Katsuda (1999) Pesticide Science
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Type 1 versus Type 2

• Type 1
• Better knockdown

• Type 2
• Better kill

Casida (1980) Environ. Health Persp.
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Properties

• No strict parent structure
• Properties vary within the class
• Toxicity varies with conformational structure
• Generally
• Broad spectrum - selectivity between pest and
  nat. enemy
• Toxic to fish, but otherwise not too bad in
  nature - plankton
• Dermal irritation
• Insecticidal properties trans 2x gt cis

Acid moiety
Ester linkage
Alcohol moiety
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Toxicity of isomers

• Varies depending on conformation
• Example Cinerin I isomers to housefly

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Examples(based on modified acid moeity)
Katsuda (1999) Pesticide Science
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• Permethrin

How many isomers?

• Broad spectrum
• Raid, Dragnet, Ambush
• First marketed in 1977
• Rat oral LD50 4000 mg/kg
• House fly topical LD50 1.1 ug/g

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• Cypermethrin

How many isomers?

• Broad spectrum
• Ammo, Cymbush, Cynoff, Demon
• Rat oral LD50 250 mg/kg
• House fly topical LD50 0.35 ug/g

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• Deltamethrin

(R)
(R)

• All activity due to single isomer 1-R cis or
  trans, a-S
• Broad spectrum
• Used worldwide, but not in US
• Rat oral LD50 135-5000 mg/kg
• House fly topical LD50 0.1 ug/g

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• Fenvalerate

• Broad spectrum
• Pyrdrin, Sumicidin
• Rat oral LD50 450 mg/kg
• House fly topical LD50 4.2 ug/g

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Examples (based on modified alcohol moiety)
Katsuda (1999) Pesticide Science
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Allethrin

• 1st synthetic pyrethroid - 1948
• trans isomer most toxic (often 41 transcis
  mixture)
• 1R-trans 4(RS)(l-allethrolone d-trans acid)
  bioallethrin
• 1R-trans 4S (S) bioallethrin
• Rat oral LD50 1110 mg/kg

How many isomers?
23 8
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Phenothrin

• Sumithrin, Anvil, Duet
• Fleas, ticks, head lice - use cancelled in 2005
• Adverse side effects hair loss, death of animals

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Other examples
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• Bifenthrin

• Cotton and greenhouse ornamentals - acaricide
• Capture, Ortho Home Defense Max, Talstar
• Rat oral LD50 55 mg/kg
• House fly topical LD50 1.4 ug/g

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• Tefluthrin

• Soil insecticide
• Force
• Rat oral LD50 20-35 mg/kg

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• Esfenvalerate

• S, S isomer
• Asana
• Rat oral LD50 75-460 mg/kg

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Pyrethroid-like compound examples
Claims that pyrethroids are highly toxicity to
fish, so not used in water systems. True in the
lab, but not nature because plankton metabolize
the compounds. Some alternatives sought out.
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• Etofenprox

Notice anything about the structure?

• Broad spectrum
• Not registered in the US
• Trebon
• Rat oral LD50 gt42000 mg/kg
• House fly topical LD50 0.4 ug/g

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Silafluofen

• High insecticidal activity
• Low mammalian/fish toxicity
• LD50 trout gt1000 mg/L (permethrin 0.0025 mg/L)
• High chemical stability
• Contact/stomach poison

Katsuda (1999) Pesticide Science
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Useful nomenclature

• Pyrethrum dried flowers/plant
• Pyrethrum extract
• How many compounds in the extract?
• Pyrethrins purified isomers from crude extract
• Pyrethroids synthetic analogs of pyrethrins
• Early pyrethroids those made from 1948-1964
• Agricultural pyrethroids used in the field

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Next time

• Poisoning symptoms
• Mode of action
• Metabolism